Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)lesioned rats: Evidence for loss of its satiety effect in VMH-lesioned rats

Noriko Satoh, Yoshihiro Ogawa, Goro Katsuura, Tetsuo Tsuji, Hiroaki Masuzaki, Junko Hiraoka, Taku Okazaki, Mikio Tamaki, Minoru Hayase, Yasunao Yoshimasa, Shigeo Nishi, Kiminori Hosoda, Kazuwa Nakao

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Abstract

To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH- lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH- lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single iv (1.0 mg/rat) or intracerebroventricular (2.0 μg/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH- lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.

Original languageEnglish
Pages (from-to)947-954
Number of pages8
JournalEndocrinology
Volume138
Issue number3
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology

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    Satoh, N., Ogawa, Y., Katsuura, G., Tsuji, T., Masuzaki, H., Hiraoka, J., Okazaki, T., Tamaki, M., Hayase, M., Yoshimasa, Y., Nishi, S., Hosoda, K., & Nakao, K. (1997). Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)lesioned rats: Evidence for loss of its satiety effect in VMH-lesioned rats. Endocrinology, 138(3), 947-954. https://doi.org/10.1210/endo.138.3.4989